Changes in the Distribution of HIV Type 1 Subtypes D and A in Rakai District, Uganda Between 1994 and 2002

Abstract

HIV-1 subtype D (HIV-1D) progresses to disease faster and has lower transmissibility than subtype A (HIV-1A). We examined whether these differences could lead to a population level change in the distribution of these subtypes over time. HIV-1 viral RNA was extracted from stored serum samples from HIV-positive subjects participating in a population-based cohort study in Rakai, Uganda in 1994 and 2002. Portions of the viral proteins gag and gp41 were sequenced and subtyped. HIV-1 subtype assignments were generated for 773 subjects in 1994 and 812 subjects in 2002. The change in subtype distribution of the population as a whole as well as quartile age groups were examined for significant changes using a linear model. There was a significant decrease in the proportion of subjects infected with HIV-1D from 70.2% to 62.4% and a significant increase in subjects infected with HIV-1A from 16.7% to 23.3% over the 8-year period ( p ¼ 0.005). The most marked changes in proportion of HIV-1D and A were seen in the younger individuals (<25 and 25-30 years; p < 0.05). The percentages of subjects infected with HIV-1C and recombinant subtypes did not change significantly. Over this 8-year period, the overall viral population in this region evolved toward the less virulent HIV-1A strain, most likely as a consequence of the faster disease progression and lower transmissibility of HIV-1D.

Identification of HIV Superinfection in Seroconcordant Couples in Rakai, Uganda, by Use of Next-Generation Deep Sequencing

“…Therefore, for the purposes of this study, 10 reads or more was the threshold for quality consensus viral sequences (see Fig. S1 in the supplemental material (5). In order to test the intra-and intersubtype viral population sensitivities of our NGS protocol, first-round PCR products targeting the p24 region from these subtype A and subtype D samples were mixed in various ratios, amplified, and sequenced on the Roche 454 system as described above (Table 1 and Fig.…”

HIV Type 1 Subtype Distribution, Multiple Infections, Sexual Networks, and Partnership Histories in Female Sex Workers in Kampala, Uganda

“…Over the years, subtype D has been more prevalent than subtype A 4,6,39 however; recent reports from Rakai district in Uganda have shown that the prevalence of subtype A has increased in this region of Uganda. 40 The Rakai study showed a significant decrease in the prevalence of subtype D from 70.2% in 1994 to 62.4% in 2002 and a significant increase of subtype A from 16.7% in 1994 to 23.3% in 2002. The observed changes in subtype prevalence over the years may have several explanations but none is entirely satisfactory.…”

Subtype-Specific Differences in Gag-Protease-Driven Replication Capacity Are Consistent with Intersubtype Differences in HIV-1 Disease Progression

“…Accordingly, subtype C is the most prevalent subtype worldwide and subtype A is the predominant subtype in East Africa (2, 3). Furthermore, reports indicate that these subtypes are increasing in prevalence (2,8,9,17).…”

“…While there is general agreement that subtype C has a transmissibility rate at least equal to those of other M group subtypes (19,20), some studies have reported increased transmissibility of subtype C compared to subtypes A and D (21)(22)(23). Furthermore, the higher heterosexual transmission of subtype A than of subtype D (24) may have contributed to the expansion of subtype A in Uganda (9).…”

“…In particular, HIV-1 subtype C, which is the most prevalent subtype globally (ϳ50% of infections), is responsible for nearly all HIV-1 infections in Southern Africa and the Ethiopia/Somalia region; it has also gained dominance in several east Asian countries and is the fastest-emerging subtype in South America (2,8). Moreover, subtypes A and D and intersubtype recombinants predominate in East and Central Africa (2, 3); subtype A in particular has significantly increased in frequency in Uganda (9).…”