HIV stigma limits the effectiveness of PMTCT in Guinea: the ANRS 12344-DIAVINA study.

BACKGROUND: Nearly half of HIV-infected children worldwide are born in West and Central African countries where access to prevention of mother-to-child transmission of HIV (PMTCT) programmes is still limited. WHO recommends reinforced antiretroviral prophylaxis for infants at high risk of mother-to-child transmission of HIV (MTCT) but its implementation needs further investigation in the field. METHODS: The prospective ANRS 12344-DIAVINA study evaluated the feasibility of a strategy combining early infant diagnosis (EID) and reinforced antiretroviral prophylaxis in high-risk infants as identified by interviews with mothers at Ignace Deen Hospital, Conakry, Guinea. RESULTS: 6493 women were admitted for delivery, 6141 (94.6%) accepted HIV testing and 114 (1.9%) were HIV positive. Among these, 51 high-risk women and their 56 infants were included. At birth, a blood sample was collected for infant EID and reinforced antiretroviral prophylaxis was initiated in 48/56 infants (86%, 95% CI 77%-95%). Iron supplementation was given to 35% of infants for non-severe anaemia. Retrospective measurement of maternal plasma viral load (pVL) at delivery revealed that 52% of women had pVL < 400 copies/mL attributable to undisclosed HIV status and/or antiretroviral intake. Undisclosed HIV status was associated with self-stigmatization (85% versus 44%, P = 0.02). Based on the results of maternal pVL at delivery, 'real' high-risk infants were more frequently lost to follow-up (44% versus 8%, P < 0.01) in comparison with low-risk infants, and this was associated with mothers' stigmatization (69% versus 31%, P < 0.01). CONCLUSIONS: Reinforced antiretroviral prophylaxis and EID at birth are widely feasible. However, mothers' self-disclosure of HIV status and antiretroviral intake do not allow adequate evaluation of MTCT risk, which argues for maternal pVL measurement near delivery. Furthermore, actions against stigmatization are crucial to improve PMTCT.

HIV-1 DNA levels in peripheral blood mononuclear cells and cannabis use are associated with intermittent HIV shedding in semen of men who have sex with men on successful antiretroviral regimens.

BACKGROUND: Few data exist on the efficacy of combined antiretroviral therapy (cART) in semen of human immunodeficiency virus type 1 (HIV-1) infected men who have sex with men (MSM) with sustained control of HIV replication in blood. METHODS: HIV-1 infected MSM on successful cART for >6 months were enrolled. HIV-RNA was quantified in seminal plasma (spVL) and in blood plasma (bpVL) from 2 paired samples collected 4 weeks apart. Relationship between spVL and bpVL (measured by an ultrasensitive assay, LOQ 10 copies/mL), total peripheral blood mononuclear cells (PBMC)-associated HIV-DNA, sexually transmitted infections (STIs), and self-reported socio-behavioral characteristics was assessed using GEE logistic regression. RESULTS: In total, 157 patients were included. Median time with bpVL <50 copies/mL was 3.3 years. spVL was detectable in 23/304 samples (prevalence 7.6%). Median spVL was 145 cp/mL (100-1475). spVL was detectable on the first, on the second, and on both samples in 5, 14, and 2 men, respectively. In sum, 33 individuals (21%) had STIs (asymptomatic in 24/33). Residual bpVL was undetectable by ultrasensitive assay in 225/300 samples (75%). After multivariable adjustments, PBMC-associated HIV-DNA (OR 2.6[1.2; 6.0], for HIV-DNA > 2.5 log10 cp/10(6) PBMC, P = .02), and cannabis use during sexual intercourse (OR 2.8[1.2; 6.7], P = .02) were the only factors associated significantly with spVL. CONCLUSION: We show that HIV-RNA can be detected intermittently in semen of HIV-1 infected MSM despite successful cART. The size of blood HIV-1 reservoir predicted spVL detection. Our results indicated also that the possible effect of cannabis should be taken into account when developing prevention interventions targeted toward HIV-infected MSM on successful cART.

Maternal 12-month response to antiretroviral therapy following prevention of mother-to-child transmission of HIV type 1, Ivory Coast, 2003-2006.

OBJECTIVE: Our aim was to study the response to antiretroviral treatment among women exposed to single-dose nevirapine (NVP) and/or short-course zidovudine (ZDV; with or without lamivudine [3TC]) for the prevention of mother-to-child transmission of human immunodeficiency virus (HIV) infection. METHODS: All HIV type 1-infected women who initiated antiretroviral treatment with stavudine or ZDV, 3TC, and NVP or efavirenz were eligible for the MTCT-Plus program in Abidjan, Ivory Coast. Exposed women had received either single-dose NVP alone or short-course ZDV (with or without 3TC) plus single-dose NVP during previous pregnancy. Genotypic resistance testing was performed at week 4 after delivery. Virologic failure was defined as a plasma HIV RNA level >500 copies/mL 12 months after initiation of antiretroviral treatment. RESULTS: Among 247 women who received antiretroviral treatment, 109 (44%) were unexposed; 81 had received short-course ZDV with 3TC, as well as single-dose NVP; 5 had received short-course ZDV plus 3TC; 50 had received short-course ZDV plus single-dose NVP; and 2 had received single-dose NVP alone. No ZDV mutation was detected in the 115 women whose specimens were available for genotypic testing; 11 (15.1%) of 73 women with 3TC exposure who were tested after delivery had 3TC resistance mutations. Three (4.3%) of 69 women exposed to short-course ZDV and 3TC plus single-dose NVP and 16 (38.1%) of 42 women exposed to short-course ZDV plus single-dose NVP had NVP resistance mutations. Antiretroviral treatment was initiated a median of 21 months after the intervention to prevent mother-to-child HIV transmission (median CD4(+) T lymphocyte count, 188 cells/mm(3)). Month 12 virologic failure was identified in 42 (19.2%) of 219 women for whom data were available, and multivariate analysis revealed that it was associated with poor adherence to treatment (adjusted odds ratio [aOR], 12.7; 95% confidence interval [CI], 3.0-53.9), postpartum 3TC resistance mutations (aOR, 6.9; 95% CI, 1.1-42.9), and a baseline CD4(+) T lymphocyte count <200 cells/mm(3) (aOR, 0.3; 95% CI, 0.2-0.8). NVP resistance was not associated with virological failure (aOR, 1.8; 95% CI, 0.5-6.5). CONCLUSIONS: Our study found that poor adherence and 3TC resistance acquired after the intervention to prevent mother-to-child transmission of HIV infection were associated with virologic failure in women who initiated antiretroviral treatment.

French national sentinel survey of antiretroviral drug resistance in patients with HIV-1 primary infection and in antiretroviral-naive chronically infected patients in 2001-2002.

OBJECTIVE: To survey the frequency of genotypic antiretroviral resistance and the spread of non-B subtypes in patients with primary HIV-1 infection (2001-2002) and in treatment-naive chronically HIV-1-infected patients (2001). METHODS: Plasma samples from 303 patients with acute HIV-1 infection (Primo study) and 363 treatment-naive patients with chronic HIV-1 infection (Odyssee study) were tested for genotypic resistance. Resistance mutations were identified from the International AIDS Society Resistance Testing-USA panel and resistant viruses were defined according to the French Agence Nationale de Recherches sur le SIDA (ANRS) resistance algorithm. RESULTS: In the Primo study, 14% of the patients had viruses with resistance mutations and 12% of patients had viruses with mutations conferring resistance to least 1 antiretroviral drug. Thirty patients had viruses with mutations to at least 1 antiretroviral drug in a single pharmacologic class. Six patients were infected by viruses resistant to 2 or 3 classes of drugs. In the Odyssee study, the prevalence of reverse transcript (RT) associated and major protease inhibitor-associated mutations was 6.1% (95% CI: 3.6-8.6). Six patients had viruses resistant to at least 1 antiretroviral drug and 3 patients had viruses resistant to 2 classes of antiretroviral drugs. Twenty-four percent of acutely infected patients harbored non-B subtype strains (19% in 1999-2000) and 33.2% of chronically infected patients (10% in 1998; P < 0.0001). CONCLUSION: In France, the frequency of HIV-1 resistance in untreated patients was not significantly higher in 2001-2002 than in previous surveys while the prevalence of non-B subtypes is increasing.

Selection of a rare resistance profile in an HIV-1-infected patient exhibiting a failure to an antiretroviral regimen including tenofovir DF.

The human immunodeficiency virus type 1 (HIV-1) resistance profile, K65R, K70E and M184V, on reverse transcriptase gene was associated with the virologic rebound consecutively to the switch of lopinavir/r to tenofovir DF in a stable regimen with nucleoside backbone of abacavir, lamivudine and didanosine. The high selective pressure on the same resistance pathway was probably associated with the loss of antiviral potency, even in well-controlled patient.