HIV-1 DNA decay is faster in children who initiate ART shortly after birth than later.

INTRODUCTION: There is limited data in children on whether persistence of HIV-1 infected cells is affected by age at initiating antiretroviral therapy (ART), its duration or any subsequent ART interruption. We therefore investigated the effects of both age of ART initiation and duration of ART interruption on HIV-1 DNA decay in children. METHODS: We investigated HIV-1 DNA decay in three groups of children on ART: Group-1 (n = 7) started uninterrupted ART within eight days of life; Group-2 (n = 8) started uninterrupted ART at a median of five months of age; and Group-3 (n = 23) started ART at a median age of 1.8 months for either 40 or 96 weeks, then interrupted ART (median of seven months), and restarted ART based on CD4 count and clinical criteria. Total HIV-1 DNA was assayed using a sensitive HIV-1 subtype C-adapted quantitative PCR for integrase. The duration of ART was square root transformed to fit the observed slowing of HIV-1 DNA decay rate. For each group, point estimates for decay rates were determined after six months of continuous suppressive ART in groups 1 and 2 or six months after restarting ART in Group-3. Groups-2 and 3 were combined using a mixed effect regression model to investigate covariates of HIV-1 DNA decay rate. RESULTS AND DISCUSSION: At six months of continuous suppressive ART, the HIV-1 DNA t½ (95% CI) was shorter in Group-1 (n = 7): 2.7 months (2.1 to 3.8), than 9.2 months (7.4 to 12.1) in Group-2 (n = 8); and 9.6 months (7.6 to 12.6) in Group-3 (n = 23) (p < 0.01). In multivariable analyses, HIV-1 DNA before treatment (p < 0.001) and the change in HIV-1 DNA during interruption (p < 0.01) were independent predictors of slower HIV-1 DNA decay. CONCLUSIONS: These data suggest that ART initiation within the first week of life can reduce the persistence of long-lived infected cells. Delaying ART is associated with slower decay of infected cells.

Rapid decline of HIV-1 DNA and RNA in infants starting very early antiretroviral therapy may pose a diagnostic challenge.

OBJECTIVE: Birth diagnosis of HIV-1 infection offers an ideal opportunity for early antiretroviral therapy (ART) to limit HIV-1 reservoir size and limit disease progression. Although data on cellular HIV-1 DNA decay exist for children commencing treatment from 2 to 3 months of age, data are lacking for starting shortly after birth. DESIGN: We studied infants who initiated ART within 8 days after birth to assess HIV-1 DNA levels longitudinally. METHODS: Children were recruited from public health clinics in Cape Town where birth diagnosis of HIV-1 coupled with early ART initiation occurred. Total cellular HIV-1 DNA levels were determined using a sensitive quantitative PCR targeting a conserved region in integrase. RESULTS: Of 11 infants diagnosed and beginning ART within 8 days of birth with detectable pre-ART HIV-1 DNA, three subsequently had undetectable HIV-1 DNA after 6 days, 3 months and 4 months on treatment, respectively. In seven who had virologic suppression (defined as a continuous downward trend in plasma HIV-1 RNA, and <100 copies/ml after 6 months) total HIV-1 DNA continued to decay over 12 months [mean half-life of 64.8 days (95% confidence interval: 47.9-105.7)]. CONCLUSION: In infants initiated on ART within 8 days of life the combination of maternal ART, and early ART for prophylaxis and treatment contribute to rapid decline of HIV-1 infected cells to low or undetectable levels. However, rapid decline of HIV-1 RNA and DNA may complicate definitive diagnosis when confirmatory testing is delayed.

Combination antiretroviral therapy reduces the detection risk of cervical human papilloma virus infection in women living with HIV.

OBJECTIVE: Data on the effect of combination antiretroviral therapy (cART) on cervical human papilloma virus (HPV) infection are both limited and conflicting. We aimed to determine the effect of the initiation of cART for HPV genotype detection on cervical samples in HIV-infected South African women. DESIGN: Prospective cohort study. METHODS: Generalized estimating equation was performed to estimate parameters of mixed-effects logistic regression models of cART on HPV cervical detection risk, adjusting for time-dependent covariates CD4 T-cell count, sexual activity and excision treatment. Ratio of odds ratios (ORs) was computed to compare the pooled cART effect on lower vs. high-risk HPV genotype groups, to the effect of cART on the risk of HPV-16 detection. RESULTS: Of the 300 patients, 204 (68%) were commenced on ART during follow-up, as they met the criteria for cART initiation. cART significantly reduced the risk for detection of HPV by 77% [OR 0.23, 95% confidence interval (CI) 0.15-0.37]. cART significantly reduced the risk of HPV-16 detection (OR 0.50, 95% CI 0.37-0.67). Every month on cART significantly reduced the detection risk of any HPV type by 9% (OR 0.91, 95% CI 0.89-0.94). The protective effect of cART on the detection risk for the low-risk HPV genotype group was significantly less than the protective effect of cART on the detection risk of HPV-16 (ratio of ORs 1.35, 95% CI 1.22-1.50). CONCLUSION: cART significantly reduced cervical HPV infection. This effect was dependent on the duration of exposure to cART and is the mechanism by which cART may improve the outcome of dysplasia in HIV-infected women.

HIV-1 subtypes B and C unique recombinant forms (URFs) and transmitted drug resistance identified in the Western Cape Province, South Africa.

South Africa has the largest worldwide HIV/AIDS population with 5.6 million people infected and at least 2 million people on antiretroviral therapy. The majority of these infections are caused by HIV-1 subtype C. Using genotyping methods we characterized HIV-1 subtypes of the gag p24 and pol PR and RT fragments, from a cohort of female participants in the Western Cape Province, South Africa. These participants were recruited as part of a study to assess the combined brain and behavioural effects of HIV and early childhood trauma. The partial HIV-1 gag and pol fragments of 84 participants were amplified by PCR and sequenced. Different online tools and manual phylogenetic analysis were used for HIV-1 subtyping. Online tools included: REGA HIV Subtyping tool version 3; Recombinant Identification Program (RIP); Context-based Modeling for Expeditious Typing (COMET); jumping profile Hidden Markov Models (jpHMM) webserver; and subtype classification using evolutionary algorithms (SCUEAL). HIV-1 subtype C predominates within the cohort with a prevalence of 93.8%. We also show, for the first time, the presence of circulating BC strains in at least 4.6% of our study cohort. In addition, we detected transmitted resistance associated mutations in 4.6% of analysed sequences. With tourism and migration rates to South Africa currently very high, we are detecting more and more HIV-1 URFs within our study populations. It is still unclear what role these unique strains will play in terms of long term antiretroviral treatment and what challenges they will pose to vaccine development. Nevertheless, it remains vitally important to monitor the HIV-1 diversity in South Africa and worldwide as the face of the epidemic is continually changing.