Emerging recombinant human immunodeficiency viruses: uneven representation of the envelope V3 region.

OBJECTIVE: To determine whether the envelope V3 region from HIV-1 subtypes A, C or D had the same probability of being present in intersubtype recombinant genomes. MATERIALS AND METHODS: The envelope C2-C5 and the gag p24-p7 regions from one hundred infants infected perinatally in Tanzania were compared using phylogenetic and recombination analysis. Exact binomial and Fisher's exact tests were used to assess if various genomic regions were more likely to be overrepresented in intersubtype recombinants. RESULTS: Of one hundred HIV-1 positive infants analyzed, twenty-two (22%) showed exclusively subtype A sequence in gag and env. Subtype C accounted for twenty-two infants (22%) whereas nineteen infants (19%) were infected by HIV-1 subtype D. Intersubtype recombinant genomes accounted for thirty-seven infections (37%). The V3 region from subtype A was found in all fifteen A-D recombinants (P = 0.00003) and the V3 region from subtype C was found in all twelve C-D recombinants (P = 0.0002). Conversely, subtype D gag sequences were preferentially represented in the gag of A-D recombinants (P = 0.0003) as well as C-D recombinants (P = 0.002). In A-D recombinants, the V3 region of subtype A was generally surrounded by subtype A C3-C5 sequences. In contrast, the V3 region from subtype C was surrounded by subtype D C3-C5 sequences in C-D recombinants. Significant differences were not found in the number of subtype A or subtype C sequences in A-C recombinants. CONCLUSION: We have shown that several recombinant HIV-1 viruses have been generated and efficiently transmitted to infants in Tanzania. The recombination patterns showed that the V3 region of subtypes A or C was always selected in A-D and C-D recombinants. This selection suggests that the fitness of subtype D-V3 in perinatal transmission may be reduced with respect to V3 from subtype A and/or subtype C. The elevated number of recombinants transmitted perinatally suggests that co-infection or super-infection by two HIV-1 subtypes is not uncommon in this population.

A cross-sectional study of a program for HIV infection control among public house workers.

We report results of a cross-sectional study of a program for human immunodeficiency virus (HIV) infection control among public house workers in Dar es Salaam. Forty percent of the 605 workers sampled had been part of this program, which included behavioral counseling and provision of condoms, for 1 year. The remaining 60% were new recruits. Program participation was associated with both enhanced condom use (p less than 0.001) and behavioral modification (p less than 0.001). Females, and specifically barmaids, were more likely to be condom users but were less likely to have changed their behavior in other respects. Seropositivity to both HIV and Treponema pallidum tended to be higher among females, especially the barmaids. Since barmaids and waitresses in public houses in Dar es Salaam often engage in prostitution, it is felt that to effect a reduction of numbers of their sexual partners, there is a need to address the social and economic factors underlying high-risk sexual behavior.

A new human immunodeficiency virus type 1 circulating recombinant form from Tanzania.

It is becoming increasingly important to identify and to study human immunodeficiency virus type 1 (HIV-1) circulating recombinant forms (CRFs) with evidence of epidemic spread, since mosaic strains arise frequently, especially in populations where multiple subtypes cocirculate. We describe the almost complete nucleotide sequence of 3 subtype C and D recombinant viruses, selected from a pool of 13 D(gag)-D/C/D(env) perinatally infected infants from Dar es Salaam, Tanzania. All three genomes had cross-over points with approximately the same genomic localization. The subtype C-like sequences were located within pol, vif, vpr, vpu, the first exons of rev and tat, V3, and the U3-R regions of the LTR. Phylogenetic analyses of the full-length genomic sequences from these viruses showed the formation of a distinct subcluster on the HIV-1 subtype D branch. The pattern of recombination of genomes belonging to this new CRF, named CRF10_CD, might have resulted from independent recombination events occurring at high frequency or from a single source that originated earlier in this population. Future surveys will be needed to determine the potential of this CRF for epidemic spread.

HIV type 1 V3 serotyping of Tanzanian samples: probable reasons for mismatching with genetic subtyping.

HIV-1 V3 serotyping is used to classify immunodeficiency viruses on the basis of antibody binding to V3 peptides derived from env genetic subtypes. Although it shows a reasonable overlap, it has been reported to be distinct from viral genetic subtypes. The aim of this study is to determine the feasibility of HIV-1 serotyping to predict genetic subtypes in an East African setting, where multiple HIV-1 subtypes have coexisted for many years. HIV-1 genetic subtypes of 86 AIDS patients in Mbeya Town, southwest Tanzania, were determined, using env nucleic acid sequencing as the basis for comparison. Those data were compared with V3 serotyping results obtained by four different methodologies. Four HIV-1 genetic subtypes were identified, including A (25, 29%), C (47, 55%), D (13, 15%), and G (1, 1%). The sensitivity and specificity of those serotyping assays varied considerably: sensitivity for genetic subtype A (40-48%), C (52-96%), and D (9-31%); and specificity for genetic subtype A (77-95%), C (46-63%), and D (97-100%). We further tried to identify reasons for the discrepancies between serotyping results and genetic subtypes. By means of logistic regression analysis three amino acid residues within the V3 loop (positions 12, 13, and 19; V, H, and A for serotype A, I, R, and T for serotype C) were found to be most important for antibody binding; a deviation from the subtype-specific amino acids was highly related to mismatched results. In addition, we have shown that phenetic analysis of V3 amino acid sequence data could be used to predict the majority of V3 serotypes (93-94%). Our data demonstrated that for the majority of specimens HIV-1 V3 serotyping results closely match the subtype of the analyzed sample as revealed by the V3 loop amino acid sequence. However, our data demonstrate that HIV-1 serotyping is not sufficiently accurate to predict genetic subtypes in Tanzania, where subtypes A, C, D, and G are circulating. This was due to highly similar amino acid sequences throughout the prevalent genetic subtypes, which caused the inability of HIV-1 V3 serotyping to differentiate subtype A from C as well as D from C. Instead, the serotyping results reflect the frequency distribution of V3 serotypes. To investigate HIV-1 genetic subtypes in population-based studies in this African setting additional or modified algorithms are needed.

PIP: HIV-1 V3 serotyping is used to classify immunodeficiency viruses on the basis of antibody binding to V3 peptides derived from env genetic subtypes. Findings are reported from a study conducted to determine whether HIV-1 serotyping could be effectively used to predict genetic subtypes in an East African setting, where multiple HIV-1 subtypes have coexisted for many years. The HIV-1 genetic subtypes of 86 people with AIDS in Mbeya Town, southwest Tanzania, were determined, using env nucleic acid sequencing as the basis for comparison. Those data were then compared with V3 serotyping results obtained by analysis with tests manufactured by Behring and the Pettenkofer Institute, tests conducted by St. Mary's Hospital Medical School, tests conducted by Georg-Speyer-Haus, and tests conducted by Universite Francois Rabelais. The following HIV-1 genetic subtypes were identified: 25 cases of A (29%), 47 of C (55%), 13 of D (15%), and 1 of G (1%). The sensitivity and specificity of the serotyping assays varied considerably. These data indicate that HIV-1 serotyping is not accurate enough to predict genetic subtypes in Tanzania. This conclusion was reached based upon the highly similar amino acid sequences throughout the prevalent genetic subtypes, which caused the inability of HIV-1 V3 serotyping to differentiate subtype A from C as well as D from C. The serotyping results instead reflect the frequency distribution of V3 serotypes.

Neuropathology of human immunodeficiency virus 1 infection. Significance of studying in forensic autopsy cases at Dar es Salaam, Tanzania.

OBJECTIVE: In sub-Saharan Africa, only a few studies of neurologic complications of human immunodeficiency virus 1 (HIV-1) infection have been done. The authors studied neuropathology of HIV-1 infection in Tanzania. DESIGN: Forensic autopsy study at Dar es Salaam, Tanzania. SETTING: A joint research project between Dar es Salaam, Tanzania, and Kumamoto, Japan. PATIENTS: Thirty patients with risk factors for HIV-1 infection. MAIN OUTCOME MEASURES: Human immunodeficiency virus 1 infection was evaluated by HIV-1 antibody test on postmortem serum samples. The brains of HIV-1-infected persons were studied histopathologically. RESULTS: Infection with HIV-1 was identified on postmortem serum samples in 10 of 30 forensic autopsy cases. Neuropathologic changes of the brain were observed in 8 of the 10 HIV-1-infected persons; these changes consisted of lymphocytic meningitis, bacterial meningoencephalitis, cryptococcal meningoencephalitis, tuberculous meningitis with brain abscesses, and intracerebral hemorrhage. CONCLUSIONS: Because none of the persons studied was suspected to have had brain diseases before autopsy, the results suggest that brain diseases of HIV-1-infected patients are likely to go unrecognized in Tanzania. In addition, the high incidence of neuropathologic findings in HIV-1-infected persons indicates that HIV-1-related brain diseases are common in Tanzania, as they are in developed countries. Further forensic autopsy study will determine the range and prevalence of brain complications and have immediate impact on the management of HIV-1-infected patients in Tanzania and other developing countries.

Susceptibility pattern of uropathogenic gram negative bacilli to antimicrobial chemotherapeutic agents in a National Hospital in Dar es Salaam.

In a period of two months, 232 consecutive urinary tract pathogens were isolated from hospitalised and non-hospitalised patients. Among the isolates, 200 (86.2%) were gram negative bacilli, including E. coli 109 (54.5%), Klebsiella species, 44 (22.5%), Enterobacter species 19 (9.5%), Proteus species 18 (9%), Morganella morganii 9 (4.5%) and Salmonella typhimurium, one (0.5%). Antimicrobial susceptibility testing to amoxycillin/clavulanic acid, nitrofurantoin, gentamicin and cefuroxime was performed using Stoke's method. Among the 109 E. coli isolates, 107 (98.2%), 104 (94.5%), 105(95.5% and 107 (98.2%) were sensitive to amoxycillin/clavulanic acid, cefuroxime, nitrofurantoin and gentamicin, respectively. Of the 44 Klebsiella isolates, 42 (95.5%), 41 (95.5%), 40 (90.9%) and 34 (77.3%) were sensitive to amoxycillin/clavulanic acid, cefuroxime, nitrofurantoin and gentamicin, respectively. There was no significant difference when the suceptibility patterns of isolates from hospitalised patients were compared to those from outpatients. Although the susceptibility pattern of urinary tract pathogens to the commonly used antimicrobial agents in the hospital is still favourable, there is a need to establish strategies to prevent emergence of resistant bacterial strains.

Bacteriology of chronic otitis media in Dar es Salaam, Tanzania.

OBJECTIVES: To determine the aetiology of chronic otitis media (COM) in Dar es Salaam and to find out the shelf life of boric acid in spirit ear drops (BAISED). DESIGN: Cross-sectional study. SETTING: Muhimbili Medical Centre and selected primary schools within Dar es Salaam. MAIN OUTCOME MEASURES: Bacterial isolates and their sensitivity patterns and shelf life of BAISED. SUBJECTS AND METHODS: One hundred and seventy six pus swab specimens obtained from 150 patients with COM for more than three months were submitted for culture and antimicrobial sensitivity testing in 1997. RESULTS: The isolates included Pseudomonas aeruginosa (51.7%), Staphylococcus aureus (17.2%), Proteus mirabilis (13.2%), Klebsiella spp. (8.0%), Escherichia coli (5.8%) and unidentified coliforms in 4.0%. All isolates were sensitive to gentamicin. Sensitivity of Pseudomonas aeruginosa and Proteus mirabilis to kanamycin was 98.5% and 100%, respectively. P. aeruginosa was sensitive to chloramphenicol, ampicillin and tetracycline by 58.1%, 10.1% and 8.3%, respectively. Three per cent BAISED inhibited the growth of all Pseudomonas aeruginosa even after it has been stored at room temperature for six weeks. CONCLUSION: Based on these results, the drug of choice for management of COM in Dar es Salaam is gentamicin. However, given its ototoxicity effects and the fact that BAISED is effective and affordable, the later should be the treatment of choice.

Predictors of CD4+ lymphocyte count among HIV-seropositive and HIV-seronegative pregnant women in Dar es Salaam, Tanzania.

OBJECTIVE: To determine the predictors of CD4+ lymphocyte count among pregnant women in Dar es Salaam, Tanzania. METHODS: Between 04/1995 and 03/1997, HIV-seropositive (n=1,027) and HIV-seronegative (n=280) pregnant women were interviewed to obtain socio-demographic characteristics. Later, blood samples was collected for determination of T-lymphocyte subsets and other haematological indices. RESULTS: CD4+ lymphocyte count was significantly higher among HIV-seronegative women (mean=770 cells/mm3, standard deviation (SD)=232 cells/mm3) than HIV-seropositive women (mean=422 cells/mm3, SD=205 cells/mm3). Most HIV-seropositive women were asymptomatic, in WHO clinical stage 1 (84.3%). Among HIV-seropositive women, total white blood count (WBC) and erythrocyte sedimentation rate (ESR) remained significantly correlated with CD4+ after adjusting for other predictors in multivariate analyses. For women of average age 25 years, the CD4+ lymphocyte count increased by about 16 cells/mm3 for each increment of 1000 WBC cells/mm3, while each 10 mm/hr increase in ESR was associated with a reduction of CD4+ lymphocyte count of about 8 cells/mm3. CONCLUSION: These results show that simple and inexpensive haematological indices cannot be recommended for use as alternative measures of HIV-related immunosuppression in this population of mainly asymptomatic women.

High frequency of sexually transmitted diseases among pregnant women in Dar es Salaam, Tanzania: need for intervention.

In order to determine the prevalence and characteristics of sexually transmitted diseases (STDs) in pregnant women (PW) attending a primary health care antenatal clinic (ANC) in metropolitan Dar es Salaam, Tanzania, a randomly selected sample of PW in their second or third trimesters were invited to participate at their first visit. They were interviewed using a questionnaire and underwent genital examination. Genital swabs were obtained for microscopy and/or culture isolation of Candida albicans, Trichomonas vaginalis, and Neisseria gonorrhoeae. Blood specimens were also obtained for serological testing for syphilis and for antibodies to the human immunodeficiency virus (HIV). A total of 777 PW aged 14 to 40 years were seen. Parities ranged from 0 to 10. Prevalence of syphilis, trichomoniasis, gonorrhoea and HIV infection were 4.0%, 22.7%, 3.6% and 15.2%, respectively. At least one acute STD (excluding HIV infection) was found in 32.8% of the PW. The prevalence of multiple STDs (excluding HIV infection) was higher in teenagers (45.3%, 77/170) than in PW in other age groups (29.2%, 177/607) (p < 0.001). The prevalence of HIV infection in teenage PW was 10.0%. Most STDs were least prevalent in PW who were married monogamously. Of the 732 PW who had one or more genital infections (including infection with Candida species), 669 (91.4%) had one or more genital complaints. However, most of the genital complaints were not disease specific. Since this study has shown that the prevalences of acute STDs were high in PW, especially in teenagers, it is recommended that all PW in Tanzania should be screened for STDs syndromically including the use of appropriate clinical and laboratory examination whenever possible.

PIP: A survey of 777 randomly selected pregnant women attending an antenatal clinic in Dar es Salaam, Tanzania, in 1993 revealed a high prevalence of sexually transmitted diseases (STDs), particularly among teenagers. The median age of survey respondents was 23.6 years (range, 14-40 years); 170 women (22%) were teenagers and 439 (56.7%) were married. 320 women (41.2%) had 1 or more STDs (excluding human immunodeficiency virus (HIV) infection); in 32.7%, there was active infection. STD prevalence was 45.3% in teenagers compared with 29.2% in adults. In the overall sample, the prevalences of syphilis, trichomoniasis, gonorrhea, and HIV were 4.0%, 22.7%, 3.6%, and 15.2%, respectively. 80 women (10.3%) showed serologic evidence of past syphilis infection and 4% had active syphilis. Syphilis was most prevalent in pregnant women aged 35 years and above (13.8%), while trichomoniasis was most common in teenagers (34.3%). Of the 732 pregnant women with genital infections, 63 (8.6%) were asymptomatic; when symptoms did exist, they were generally not disease-specific. The most significant risk factor for STDs, including HIV, was single marital status. These findings suggest a need for the introduction of essential clinical and laboratory facilities for STD detection to antenatal clinics in Tanzania.

Susceptibility pattern of Neisseria gonorrhoeae to antimicrobial agents in Dar es Salaam.

OBJECTIVE: To determine the susceptibility pattern of local strains of Neisseria gonorrhoeae from Dar es salaam, Tanzania to locally used antibiotics. METHOD: Out of 429 Neisseria gonorrhoeae strains isolated between 1993 and 1995, one hundred and ninety nine were recovered and tested. Minimum inhibitory concentrations (MIC) of penicillin, doxycycline, erythromycin, cefuroxime and ciprofloxacin were determined by the E-test method while that of spectinomycin was measured by the agar dilution method. Penicillinase producing N. gonorrhoeae were identified by the chromogenic cephalosporin method. RESULTS: Of the 199 strains tested 128 (64%) were found to be penicillinase producing Neisseria gonorrhoeae (PPNG). Only 19 (10%) were penicillin sensitive while all penicillin resistant strains were found to be PPNG. One hundred and seventy five (88%), 11(5%) and 13 (7%) of the tested isolates were resistant, less susceptible and fully susceptible to doxycycline respectively. Resistance to cotrimoxazole, cefuroxime and ciprofloxacin was 36 (18%), 11 (6%), and 3 (2%) respectively. The trend of antibiotic susceptibility rates over the three year period of study showed a significant increase in the proportion of susceptible strains to cotrimoxazole. All of the 75 strains tested against spectinomycin were susceptible. There was a statistically significant difference between the susceptibility patterns of non-PPNG and PPNG. Non-PPNG isolates were more susceptible to doxycycline (chi 2 = 78.2, df 2, p = < 0.0001). CONCLUSION: These findings have shown that spectinomycin, ciprofloxacin and cefuroxime could continue to be used to treat gonorrhoea in our settings. Continuous surveillance of susceptibility to the commonly used antibiotics is important in order to detect emergence of resistance early and control the possible wide spread of resistant strains.

PIP: This article presents a study on the susceptibility pattern of local strains of Neisseria gonorrheae (NG) to antimicrobial agents (penicillin, doxycyline, erythromycin, cefuroxime, ciprofloxacin, cotrimoxazole, and spectinomycin) in Dar Es Salaam, Tanzania. Out of the 429 isolated strains of NG in 1993-95, 199 were included in the study. Susceptibility patterns to the six antimicrobials was determined through the E-test method, a test that measures their minimum inhibitory concentrations (MICs). On the other hand, the spectinomycin MIC was determined through the antibiotic agar dilution method. Results revealed the following patterns of susceptibility of isolates: spectinomycin (100%), ciprofloxacin (97%), Cefuroxime (89%), erythromycin (57%), cotrimoxazole (40%), doxycycline (7%), and penicillin (10%). It was also noted that NG strains are highly resistant to penicillin (64%) and doxycycline (88%). The study concludes that three drugs--spectinomycin, ciprofloxacin, and spectinomycin--could be effective in treating gonorrhea. However, a continued surveillance of common antibiotics against gonococcus is necessary for the early detection and control of strain resistance.

The use of total lymphocyte count as a surrogate for low CD4+ T lymphocyte cell counts among HIV-1-infected women in Tanzania.

BACKGROUND: Human Immunodeficiency Virus type 1 (HIV-1) infection leads to a progressive decline in CD4+ T-lymphocyte (CD4) cells. Initiation of prophylaxis against Opportunistic infections in adults (CD4% used for children) and antiretroviral therapy is usually based on CD4 cell counts, but CD4 cell counts measurement is not affordable in most African countries. OBJECTIVE: To examine whether total lymphocyte counts (TLC) may be used as proxies for low CD4 cell counts. DESIGN: Cross-sectional at baseline when women were pregnant and at least six months postpartum. METHODS: 1,078 HIV-1-infected pregnant women from Dar es Salaam, Tanzania were enrolled in a randomized clinical trial. A series of receiver operator characteristic (ROC) curves were created at baseline and at least 6 months postpartum and among women in WHO Stage 3 and above. The sensitivity and specificity of TLC and hemoglobin in predicting an absolute CD4 count < 200 cells/mm3 were determined for various clinically relevant cut points. RESULTS: TLC was not a good predictor of low CD4 cell counts during pregnancy or at least six months postpartum as exhibited by low ROC Area Under the Curve (AUCs) of .57 and .62 respectively. No other variable had the ability to predict CD4 < 200 cells/mm3. CONCLUSIONS: The use of TLC as a proxy for the estimation of low CD4 cell counts in a population of HIV-1-infected adults from sub-Saharan Africa was not substantiated. Inexpensive methods to quantify CD4 cell counts in Africa are needed.

Prevalence of, and risk factors for, HSV-2 antibodies in sexually transmitted disease patients, healthy pregnant females, blood donors and medical students in Tanzania and Norway.

The prevalence of specific HSV-2 antibodies was studied in Tanzanian and Norwegian sexually transmitted disease (STD) patients (1095) and non-STD patients (488). Correlates to demographic and behavioural factors were evaluated. Seropositivity was determined by the non-commercial peptide-55 enzyme-linked immunoassay. The prevalence of HSV-2 antibodies was 70% in Tanzanian and 17% in Norwegian STD patients, 35% in Tanzanian blood donors and pregnant women, and 4, 7 and 14% in Norwegian medical students, blood donors and pregnant women respectively. A higher HSV-2 prevalence was associated with female sex, increasing age, previous STDs, history of genital HSV infection, coitarchal age (age at first intercourse) <15 years and HIV seropositivity. Compared to previous data, the prevalence of HSV-2 antibodies in Tanzanian STD patients has increased remarkably. In Norwegian STD patients our results are consistent with, or lower than, the prevalence previously reported in Western Europe. Demographic rather than behavioural factors were associated with higher prevalence of HSV-2 antibodies in STD patients.

Sexual behaviour among youths at high risk for HIV-1 infection in Dar es Salaam, Tanzania.

OBJECTIVES: To investigate sex specific sexual behaviour in youths visiting a youth clinic for sexual and reproductive health in Dar es Saalam. METHODS: A questionnaire was administered to a random sample of youths between 10 and 24 years of age attending the youth health clinic in Dar es Saalam. The clinical investigation included testing for syphilis and HIV-1 antibodies RESULTS: 1423 youths attended the clinic between September 1997 and August 1998. The study population comprised 213 (53.5%) males and 185 (46.5%) females. 97 (24.4%) were below 20 years. The mean age at coitarche was 16.5 and 17.0 years of age for males and females, respectively. The coitarche was involuntary in 15 females (8.6%). 49.5% males reported more than five lifetime partners compared with 14.1% for females (p<0.0001). Males reported recent partners to be 2.5 years younger, while females reported them to be 5.0 years older. No contraceptive use was reported by 29.7% of the males and 40.3% of females. 52.7% females had been pregnant and 26 (14.1%) reported induced abortions. Genital discharge was found in 69.5% and 73.9% and GUD in 36.6% and 27.1% of males and females respectively. 12 males (5.9%) and 43 females (24.6%) were found to be HIV-1 infected. 13.8% of the females with only one lifetime partner were HIV-1 infected compared with 40.9% with more than five partners (p = 0.028). CONCLUSIONS: Many youths in Dar es Salaam engage in sexual behaviours that put them at risk of unwanted pregnancies and STIs including HIV infection. Female youths were more likely to contract HIV infection than males. In African urban areas youth oriented clinics can have a pivotal role in HIV/STI prevention and control

Transmission of human immunodeficiency type 1 viruses with intersubtype recombinant long terminal repeat sequences.

Retroviruses such as human immunodeficiency virus type 1 (HIV-1) contain two RNA strands per virion, and recombination can occur frequently during reverse transcription. Recombination may occur between HIV-1 genomes of the same subtype or among genomes of two or more distinct subtypes present in an individual. In the current study, we found that recombinatorial events were not limited to viral structural genes such as gag and env, but rather, recombination could likewise occur within the 5' long terminal repeat (LTR). Intersubtype recombinant LTRs among HIV-1 subtypes A, C, and D were found in Tanzanian infants. By introducing novel LTR sequences, these recombinant LTR viruses may further increase the adaptive potential and fitness of HIV-1.

Differences in perinatal transmission among human immunodeficiency virus type 1 genotypes.

OBJECTIVE: To determine whether genotypes from human immunodeficiency virus type 1 (HIV-1) subtypes A, C, or D or intersubtype recombinants have the same probability of being transmitted from mother to child. METHODS: We determined the HIV-1 genetic subtype and maternal risk factors of 51 matched transmitting and nontransmitting mothers from Tanzania. The HIV-1 gag (p24-p7) and env (C2-C5) nucleotide sequences were used for genotype classification, and matched logistic regression analysis was used to assess differences among genotypes. RESULTS: Mothers infected with HIV-1 subtype A (odds ratio, 3.8; 95% CI, 0.8-24.7%), HIV-1 subtype C (odds ratio, 5.1; 95% CI, 1.3-30.8%), or HIV-1 intersubtype recombinant viruses (odds ratio, 5.3; 95% CI, 1.2-33.4%) were more likely to transmit HIV-1 to their infants than mothers infected with HIV-1 subtype D. Lower CD4 cell counts at enrollment were associated with transmission, but CD4 cell counts within each genotype did not explain differences in transmission among HIV-1 genotypes. CONCLUSION: We have shown that HIV-1 genotypes might be associated with differential risk for vertical transmission. These findings provide the first evidence that HIV-1 genetic subtypes may play a role in rates of vertical transmission in an African setting.

HIV-1 LTR subtype and perinatal transmission.

Multiple subtypes of HIV-1 have been identified; however, there is little data on the relative transmissibility of viruses belonging to different subtypes. A matched case-control study addressed whether viruses with different long terminal repeat (LTR) subtypes were transmitted equally from mother to infant. The LTR subtype was determined for 45 matched cases and controls who participated in a clinical trial in Tanzania. HIV-1 subtypes A, C, and D and intersubtype recombinant sequences were identified. Exact matched logistic regression analysis showed that viruses containing subtype A or intersubtype recombinant LTRs were 3.2 and 4.8 times more likely to be transmitted from mother to infant than viruses with subtype D LTRs. Viruses containing subtype C LTRs were 6.1 times more likely to be transmitted than those with subtype D LTRs. These differences in transmission were independent of maternal CD4 at enrollment. Thus, it appears that HIV-1 subtype may be associated with differing rates of perinatal transmission in Tanzania.

Randomized trial of vitamin supplements in relation to vertical transmission of HIV-1 in Tanzania.

BACKGROUND: Observational studies suggest that poor nutritional status among HIV-infected pregnant women is associated with a higher risk of vertical transmission of HIV. METHODS: We randomized 1083 pregnant women infected with HIV-1 in a double-blind, placebo-controlled trial to examine the effects of supplements of vitamin A and/or multivitamins (excluding vitamin A) using a 2-x-2 factorial design. We report the effects of the supplements on HIV infection defined using polymerase chain reaction (PCR), or death up to 6 weeks postpartum. RESULTS: Of babies in the multivitamin arm 38, (10.1%) were HIV-positive at birth compared with 24 (6.6%) in the no-multivitamin arm (relative risk [RR] = 1.54; 95% CI, 0.94-2.51; p = .08). Of babies born to mothers in the vitamin A arm, 38 (10.0%) were HIV-positive at birth compared with 24 (6.7%) in the no-vitamin A arm (RR, 1.49; 95% CI, 0.91-2.43; p = 0.11). Neither multivitamins nor vitamin A had an effect on HIV status at 6 weeks among those who were HIV-negative at birth (RR = 1.04; 95% CI, 0.65-1.66; p = 0.88) and (RR = 1.30; 95% CI, 0.80-2.09; p = .29, respectively). Similarly, neither supplement was associated with being either HIV-infected or dead at birth (RR, 0.98; 95% CI, 0.76-1.27; p = .89 and RR, 1.01; 95% CI, 0.78-1.31; p = .95, respectively. A beneficial effect of multivitamins on birth weight was limited to babies who were HIV-negative at birth; babies in the multivitamin arm weighed +94 g more compared with those in the no-multivitamin arm (p = .02). Among babies who were HIV-positive at birth, the corresponding difference was -31 g (p = .82). CONCLUSIONS: Vitamin A and multivitamins did not affect the risk of vertical transmission of HIV in utero nor during the intrapartum and early breastfeeding periods. Multivitamins resulted in a significant improvement in birth weight of babies who were HIV-negative at birth but had no effect among those who were HIV-positive. The effect of vitamin supplements on HIV transmission through breastfeeding and on clinical progression of HIV disease is yet to be ascertained.

Randomised trial of effects of vitamin supplements on pregnancy outcomes and T cell counts in HIV-1-infected women in Tanzania.

BACKGROUND: In HIV-1-infected women, poor micronutrient status has been associated with faster progression of HIV-1 disease and adverse birth outcomes. We assessed the effects of vitamin A and multivitamins on birth outcomes in such women. METHODS: In Tanzania, 1075 HIV-1-infected pregnant women at between 12 and 27 weeks' gestation received placebo (n=267), vitamin A (n=269), multivitamins excluding vitamin A (n=269), or multivitamins including vitamin A (n=270) in a randomised, double-blind, placebo-controlled trial with a 2x2 factorial design. We measured the effects of multivitamins and vitamin A on birth outcomes and counts of T lymphocyte subsets. We did analyses by intention to treat. RESULTS: 30 fetal deaths occurred among women assigned multivitamins compared with 49 among those not on multivitamins (relative risk 0.61 [95% CI 0.39-0.94] p=0.02). Multivitamin supplementation decreased the risk of low birthweight (<2500 g) by 44% (0.56 [0.38-0.82] p=0.003), severe preterm birth (<34 weeks of gestation) by 39% (0.61 [0.38-0.96] p=0.03), and small size for gestational age at birth by 43% (0.57 [0.39-0.82] p=0.002). Vitamin A supplementation had no significant effect on these variables. Multivitamins, but not vitamin A, resulted in a significant increase in CD4, CD8, and CD3 counts. INTERPRETATION: Multivitamin supplementation is a low-cost way of substantially decreasing adverse pregnancy outcomes and increasing T-cell counts in HIV-1-infected women. The clinical relevance of our findings for vertical transmission and clinical progression of HIV-1 disease is yet to be ascertained.

PIP: Poor micronutrient status has been associated, in HIV-positive women, with faster progression of HIV disease and adverse birth outcomes. This randomized, double-blind, placebo-controlled study assessed the effects of vitamin A and multivitamins on birth outcomes in 1075 HIV-positive pregnant women at 12-27 weeks' gestation from Dar es Salaam, Tanzania. There were no differences in baseline plasma vitamin concentrations between groups. 267 women received a placebo, 269 were given vitamin A, 269 were administered a multivitamin excluding vitamin A, and 270 received a multivitamin including vitamin A. There were 30 fetal deaths in the group of women who received multivitamins (with and without vitamin A) compared with 49 among those not given multivitamins (relative risk (RR), 0.61; 95% confidence interval (CI), 0.39-0.94). Multivitamin supplementation decreased the risk of low birth weight (2500 g) by 44% (RR, 0.56; 95% CI, 0.38-0.82), of preterm birth (prior to 34 weeks gestation) by 39% (RR, 0.61; 95% CI, 0.38-0.96), and of small size for gestational age at birth by 43% (RR, 0.57; 95% CI, 0.39-0.82). Vitamin A had no significant effect on these variables. Multivitamins, but not vitamin A, were associated with significant increases in CD4, CD8, and CD3 counts. The clinical relevance of multivitamin supplementation for vertical transmission of HIV and the progression of disease remain unknown. However, these results indicate such supplementation is a low-cost means of substantially decreasing adverse pregnancy outcomes and increasing T cell counts in HIV-infected women. The observed beneficial effects of multivitamins on birth outcomes may have been mediated through improved maternal immune status.